Epileptogenesis and chronic seizures in a mouse model of temporal lobe epilepsy are associated with distinct EEG patterns and selective neurochemical alterations in the contralateral hippocampus

Exp Neurol. 2005 Jul;194(1):76-90. doi: 10.1016/j.expneurol.2005.01.029.


Major aspects of temporal lobe epilepsy (TLE) can be reproduced in mice following a unilateral injection of kainic acid into the dorsal hippocampus. This treatment induces a non-convulsive status epilepticus and acute lesion of CA1, CA3c and hilar neurons, followed by a latent phase with ongoing ipsilateral neuronal degeneration. Spontaneous focal seizures mark the onset of the chronic phase. In striking contrast, the ventral hippocampus and the contralateral side remain structurally unaffected and seizure-free. In this study, functional and neurochemical alterations of the contralateral side were studied to find candidate mechanisms underlying the lack of a mirror focus in this model of TLE. A quantitative analysis of simultaneous, bilateral EEG recordings revealed a significant decrease of theta oscillations ipsilaterally during the latent phase and bilaterally during the chronic phase. Furthermore, the synchronization of bilateral activity, which is very high in control, was strongly reduced already during the latent phase and the decrease was independent of recurrent seizures. Immunohistochemical analysis performed in the contralateral hippocampus of kainate-treated mice revealed reduced calbindin-labeling of CA1 pyramidal cells; down-regulation of CCK-8 and up-regulation of NPY-labeling in mossy fibers; and a redistribution of galanin immunoreactivity. These changes collectively might limit neuronal excitability in CA1 and dentate gyrus, as well as glutamate release from mossy fiber terminals. Although these functional and neurochemical alterations might not be causally related, they likely reflect long-ranging network alterations underlying the independent evolution of the two hippocampal formations during the development of an epileptic focus in this model of TLE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Animals
  • Brain Chemistry / drug effects
  • Brain Chemistry / physiology*
  • Calbindins
  • Chronic Disease
  • Disease Models, Animal
  • Down-Regulation / drug effects
  • Down-Regulation / physiology
  • Electroencephalography*
  • Epilepsy / chemically induced
  • Epilepsy / metabolism
  • Epilepsy / physiopathology*
  • Epilepsy, Temporal Lobe / chemically induced
  • Epilepsy, Temporal Lobe / metabolism
  • Epilepsy, Temporal Lobe / physiopathology*
  • Functional Laterality / drug effects
  • Functional Laterality / physiology
  • Galanin / metabolism
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hippocampus / physiopathology*
  • Kainic Acid / pharmacology
  • Mice
  • Mossy Fibers, Hippocampal / drug effects
  • Mossy Fibers, Hippocampal / metabolism
  • Nerve Degeneration / chemically induced
  • Nerve Degeneration / metabolism
  • Nerve Degeneration / physiopathology
  • Neural Pathways / drug effects
  • Neural Pathways / metabolism
  • Neural Pathways / physiopathology
  • Neuropeptide Y / metabolism
  • Neurotoxins / pharmacology
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / metabolism
  • S100 Calcium Binding Protein G / metabolism
  • Sincalide / metabolism
  • Status Epilepticus / chemically induced
  • Status Epilepticus / metabolism
  • Status Epilepticus / physiopathology
  • Theta Rhythm / drug effects
  • Up-Regulation / drug effects
  • Up-Regulation / physiology


  • Calbindins
  • Neuropeptide Y
  • Neurotoxins
  • S100 Calcium Binding Protein G
  • Galanin
  • Sincalide
  • Kainic Acid